WHO group envisions greater production of H1N1 vaccine

May 19, 2009 (CIDRAP News) – A new report from a World Health Organization (WHO) advisory group predicts that global production of vaccine for the novel H1N1 influenza virus could be as much as 4.9 billon doses a year, far higher than previous estimates.

The report also says that it's "premature" to recommend starting mass production of an H1N1 vaccine now and predicts that if the recommendation is made, production could begin no sooner than mid-July. It gives no estimate of when the first doses would become available.

The four-page report is based on a May 14 teleconference of about 40 stakeholders, called the Ad Hoc Policy Advisory Working Group on Influenza A (H1N1) Vaccines. It was released late yesterday.

The report says that vaccine makers are expected to produce about 480 million doses of seasonal flu vaccine for the northern hemisphere's 2008-09 flu season. About 350 million doses will be ready by June 30 and 430 million doses by Jul 31.

The report continues, "It is estimated that up to 4.9 billion doses [of novel H1N1 vaccine] could be produced over a 12-month period after the initiation of full-scale production," if production yields are about the same as for seasonal flu vaccines and if "the most dose-sparing formulations" are used.

The estimate of 4.9 billion doses is far above the 1 billion to 2 billion doses mentioned by the WHO's Dr. Marie-Paul Kieny at a news briefing on May 6. She said that was based on an estimated global production capacity of about 900 million doses for seasonal vaccine.

The report does not explain what the 4.9-billion-dose estimate is based on, and WHO officials did not reply to a query about this today. But the mention of dose-sparing formulations is an apparent reference to adjuvants—immune-system stimulants that, when added to a vaccine, allow doses to be diluted, thus increasing supplies.

The working group also says that with total annual production of 4.9 billion doses, the United Nations (UN) could potentially have access to 400 million doses.

The report says that a monovalent, or single-strain, vaccine is the preferred option for the H1N1 vaccine. There has been speculation about adding a novel H1N1 vaccine to the seasonal flu vaccine, which targets three flu strains, creating a four-strain vaccine that could protect against seasonal flu and the novel virus. But the report says this "would have significant regulatory implications," implying it would cause delays.

Timing considerationsConcerning production timetables, the report says that candidate vaccine viruses (seed strains) will become available to vaccine makers at the end of this month—on the later end of previous estimates, which were sometime in the second half of May. But distribution of the seed strains may need to be delayed another week or two for testing in animals to make sure they are safe.

"Typically one to two additional months are needed by manufacturers after they receive vaccine viruses to isolate rapid growing strains to [achieve] maximum yield," the report adds. "Based on these considerations, the Working Group concluded that manufacturers would not be ready to switch to large-scale production before mid-July 2009."

It adds that moving to production too quickly could lead to using strains that don't grow very well in eggs, as happened with a 2004 Vietnam strain of the H5N1 virus that was used for vaccine production.

The report does not suggest when the first vaccine doses might be ready, but health officials have said that, from the time manufacturers receive vaccine seed strains, it will probably take 4 to 6 months to start producing an H1N1 vaccine in quantity. With the vaccine viruses going to manufacturers at the end of May, that suggests that the first doses could be ready in October.

Sanofi Pasteur, the largest flu vaccine supplier for the US market in recent years, expects to be able to produce its first doses of an H1N1 vaccine within 3 to 4 months after receiving the seed strains, a company spokeswoman said today.

"Typically once we receive the seed virus, in a couple of weeks we can be ready to move to full-scale production, and in a couple of months—three to four—we believe we will have the first doses to provide to health authorities," Donna Cary, director of public relations, told CIDRAP News.

"We will have better information once we receive the seed virus and reagents and the government establishes the licensure process," she added.

GlaxoSmithKline, which also sells flu vaccine in the United States, will probably need 4 to 6 months to start providing vaccine after it receives the seed strains, company spokeswoman Sarah Alspach told CIDRAP News today. She noted that clinical trials will be necessary, and unpredictable hurdles could crop up.

The WHO report notes that many factors affecting H1N1 vaccine supplies remain unknown, including the optimal dose, the required number of doses, the required interval between doses, the interchangeability of different products, and the safety profile.

One safety issue will be the risk of Guillian-Barre syndrome, the paralytic condition that ultimately derailed the nationwide swine flu vaccination campaign in 1976, the report says. It recommends determining baseline rates of the syndrome in various populations before a pandemic vaccine is available, so that any later changes in its incidence can be detected.

Vow to help developing countriesIn other developments today, WHO Director-General Margaret Chan said vaccine company executives who met with the agency today showed a "serious commitment" to helping provide H1N1 vaccines for developing countries, but she gave no specifics on what the companies might do.

In a press release, the WHO said it would work with the UN and other groups "to find innovative funding mechanisms to ensure that developing countries were not denied access to vaccines because of lack of means."

Chan said she would meet with vaccine manufacturers individually to develop strategies to make vaccine supplies available to needy countries, according to the release.